A new oncofetal antigen (OFA-1) has been identified on biopsied and cultured human tumors of diverse histologic origin including over 50% of 170 biopsied melanomas, sarcomas, and carcinomas. OFA-1 was not detected on any of 61 normal adult tissues, but was detected on fetal brain tissues by serologic absorption. OFA-1 was induced on normal fibroblasts after in vitro culture. OFA-1 is immunogenic in man, unlike other fetal antigens (CEA and AFP), since antibody to OFA-1 is found in sera of many cancer patients and is induced in cancer patients immunized with OFA-1 positive allogeneic tumor cells. Tumor associated antigens were isolated from melanoma cells cultured in a serum-free chemically defined medium. The purified antigens were cross-reactive with other melanomas, but not with sarcomas or fetal tissues. The purified antigen was labeled with 125I and used to develop a radioimmunoassay with melanoma patients' sera. The assay will be tested for sensitivity in detecting soluble antigen in sera from advanced cancer patients and a similar assay will be developed with the oncofetal antigen. We will continue to investigate antigenic modulation and other immune mechanisms that account for survival of antigenic tumor cells in patients with high levels of antibody.